Since gene therapy of the retina depends on knowledge of normal complements of tissue-specific genes and how they change in disease, we are studying the expression of specific gene products related to several hereditary diseases. If normal mechanisms fail, hereditary diseases of the retina such as retinoblastoma or retinitis pigmentosa will result. We have developed new techniques to clone and sequence retina-specific genes at a higher efficiency. We also have found that laminin, an important extracellular matrix protein, and cAMP, a small intracellular messenger, slow retinoblastoma cell growth and promote differentiation. Specifically, they switch development from a photoreceptor-like pathway to a conventional neuronal-like pathway. Progress also has been made in identifying apoptosis as a primary and unifying mechanism for cell death in several hereditary retinal degenerations. All these factors and processes could lead to more efficient gene therapy of the diseased neural retina.